tbuckley/cabot-search huggingface dataset:
Abstract 12798: Plasma Ferritin, Incident Heart Failure Phenotypes, And Cardiac Dysfunction in Late Life: The Atherosclerosis Risk in Communities Study
Authors: Iman A Aboelsaad, Brian Claggett, Victoria Arthur, Pranav Dorbala, Kuni Matsushita, Brandon Lennep, Bing Yu, Pamela L Lutsey, Chiadi E Ndumele, Youssef M Farag, Amil M Shah, Leo Buckley
Journal: Circulation (2022)

Introduction: Iron deficiency affects 10% of adults aged 70 years or older and is associated with worse symptom burden and a higher risk of hospitalization in adults with heart failure (HF) with reduced ejection fraction (HFrEF) in mid-life. However, the relationships between iron deficiency and incident HF, HFrEF and HF with preserved EF (HFpEF) in late life remain incompletely understood. Hypothesis: Iron deficiency, as measured by lower plasma ferritin levels, is associated with an increased risk of incident HF, HFrEF, and HFpEF in older adults. Methods: We included 3,567 participants (mean age 75 years, 56% women and 14% Black) from the ongoing, ARIC study who had plasma ferritin measured by an aptamer assay (SomaLogic) and were free from prevalent HF and anemia (Hb &lt;13 for men and &lt;12 for women). The associations of log 2 -transformed plasma ferritin with adjudicated incident overall HF, HFrEF (LVEF &lt; 50%) and HFpEF were estimated using Cox proportional hazards models. The associations of plasma ferritin with echocardiographic measures of cardiac size and function at Visit 5 were estimated with linear regression models. All models were adjusted for age, sex, race, smoking, body mass index, coronary heart disease, diabetes, hypertension, atrial fibrillation and eGFR. Results: Over a median 7 years of follow-up, 312 incident HF events occurred (140 HFrEF, 137 HFpEF, 51 unknown EF). Lower ferritin level was associated with a higher risk of overall HF and HFpEF, but not HFrEF ( Figure ). Lower ferritin levels associated with a higher E/e' ratio (standardized beta [95% CI]: 0.06 [0.03-0.08]; P&lt;0.01). Plasma ferritin levels did not associate with LV mass index or measures of LV systolic function (ejection fraction, global longitudinal strain; all P &gt; 0.05). Conclusion: Lower plasma ferritin levels associate with higher LV filling pressure and greater risk of incident HF, and in particular HFpEF, in late life. Iron deficiency may contribute to the pathophysiology of HF in late life.
Abstract 12919: Stress Induced Cardiomyopathy After the Covid-19 Vaccine
Authors: Keerthana Pakanati, John Nguyen, Richard Stoebner
Journal: Circulation (2022)

Introduction: The SARS-CoV-2 virus has potential to cause acute and long-term cardiac effects. The vaccines were developed to prevent severe illness, but there are concerns about vaccine related side effects. Specific to the heart there have been case reports of mRNA vaccine related cardiomyopathies, particularly myocarditis. We present a case of a patient with presumptive stress induced cardiomyopathy in the setting of recent Covid-19 mRNA vaccination. Case Presentation: A 93-year-old female with a past medical history of hypertension presented with worsening shortness of breath and bilateral lower extremity edema. She received her second dose of the Covid-19 mRNA vaccine five days prior to presentation. She had no history of heart disease, was a nonsmoker, and denied alcohol or drug use. In the ED she was noted to be fluid-overloaded, and her CT chest showed minimal coronary calcification and bilateral pleural effusions. She was admitted for heart failure exacerbation and started on IV furosemide. Her transthoracic echocardiogram showed an ejection fraction of 40-45%. The pattern of left ventricular dysfunction was consistent with stress induced cardiomyopathy with apical akinesis and basal sparing of the left ventricular wall segments. Cardiology was consulted and recommended management with diuretics and beta blocker. She had a diuresis of 5 liters during her hospitalization. At clinic follow-up, dyspnea had improved, and her peripheral edema had resolved. Repeat echocardiogram showed recovery of left ventricular ejection fraction to 61% by Simpsons biplane technique with no regional wall motion abnormalities. Further cardiac assessment to evaluate for obstructive coronary artery disease and myocarditis was discussed and offered to the patient but was declined due to her positive response to conservative management. Discussion: The precise etiology of stress induced cardiomyopathy is unknown, but it is thought to be secondary to the sudden release of stress hormones. There are isolated reports of stress induced cardiomyopathy associated with Covid-19 vaccination, but the potential mechanism is unclear. An improved understanding of the potential effects of mRNA vaccines may help guide decisions regarding future booster vaccinations.
Abstract 13352: Differential Response of Healthy Endocardial Cells versus Endocardial Fibroelastosis-Derived Cells to Flow Alterations and Statins
Authors: Natalia Silva-Gomez, Daniel Diaz-Gil, Aimee Winkler, Sitaram Emani, Breanna L Piekarski, Pedro J Del Nido, Ingeborg Friehs
Journal: Circulation (2022)

Introduction: Endocardial Fibroelastosis (EFE) is a subendocardial thickening of organized collagen and elastin layers restricting the ventricle. It has been linked to flow disturbances in congenital heart defects. Endothelial-to-mesenchymal transition (EndMT) has been identified as the underlying mechanism for EFE and also plays a central role in other diseases such as atherosclerosis where statins (e. g. atorvastatin) have been successfully used as EndMT-inhibitors. This study sought to establish a causal relationship between flow and EndMT, and to determine the protective effects of atorvastatin. Methods: Healthy endocardial endothelial cells (EECs) and EFE-derived EECs were exposed to either flow stagnation (≤5dynes/cm 2 ) with and without atorvastatin (0.5μmol/l) or physiological flow (~10dynes/cm 2 ) using a flow pump system (ibidi). Active EndMT (double staining with αSMA and CD31/VE-Cadherin) and collagen production was determined by immunohistochemical staining. Results: In healthy EECs (n=4), flow stagnation induced EndMT and collagen production which was significantly ameliorated by physiological flow (n=3, p&lt;0.001, Fig. 1A+C). In contrast, physiological flow resulted in an increase in collagen production by 89% (n=8, p&lt;0.001, Fig. 1D) in EFE-derived EECs. Under flow stagnation, atorvastatin inhibited EndMT (reduction by 39%, p&lt;0.001, Fig. 1A) and collagen production in healthy EECs (reduction by 9%, p&lt;0.001, Fig. 1C). This effect was blunted in EFE-derived EECs regarding EndMT reduction (17%, p&lt;0.001, Fig. 1B), with no effect on collagen. Conclusion: Physiological flow and atorvastatin protect healthy EECs from EndMT but only the latter is beneficial for EFE-derived EECs. Thus, statins potentially offer a preventative treatment for EFE patients with flow stagnation. This study revealed a profound difference in the response to flow of healthy and EFE-derived EECs, indicating an intrinsic predisposition to EndMT in these patients.
Abstract 14129: The Association of Sarcopenic Obesity and Increased Arterial Stiffness
Authors: Chisa Matsumoto, Hirofumi Tomiyama, Mari Matsuura, SHIORI TAKAMIYA, Hiroki Nakano, Kazuki Shiina, Akira Yamashina
Journal: Circulation (2022)

Introduction: Both sarcopenia and obesity have been regarded as risk factors of cardiovascular disease (CVD). However, inconsistent results of the association between sarcopenic obesity (SO) and risk of CVD have been reported. Also, no studies evaluated the association of SO and arterial stiffness, a marker of CVD. The objective of this study is to evaluate the association of SO and arterial stiffness. Hypothesis: We hypothesized SO is associated with increased arterial stiffness. Methods: Japanese Subjects above 50 years old who underwent annual health-checkup were enrolled in this cross-sectional study. Subjects with history of CVD and dementia were excluded. Arterial stiffness was evaluated by brachial-ankle pulse wave velocity (baPWV). Obesity was defined as visceral fat over 100 cm2 evaluated by abdominal computed tomography. We evaluated sarcopenia by screening locomotive syndrome assessed by the questionnaires (GLFS-25) and physical performance tests consisted of those for a two-step test and a stand-up test according to the guidance of the Japanese Orthopedic Association. We defined SO as a combination of obesity and sarcopenia. The associations of SO, obesity, sarcopenia and baPWV were assessed by multivariable linear regression analysis adjusted for conventional CVD risk factors. Results: We categorized total 137 subjects (mean age: 59±6 years) into four groups; subjects with SO (N=28), only sarcopenia (N=37), only obesity (N=2), and none of them (N=43). BaPWV in subjects with SO was highest compared to other three groups (Figure, p=0.048). Multivariable linear regression analysis revealed that SO, sarcopenia, obesity, were gradually associated with increased arterial stiffness independent of CVD risk factors including lipid and glucose metabolism. (β=48±20, p=0.01). Conclusion: SO was associated with increased arterial stiffness independent of conventional CVD risk factors. Further research on SO and CVD is warranted.
Abstract 13998: Glycemic Control and Prognosis in Patients With Type 2 Diabetes Mellitus Hospitalized for Decompensated Heart Failure With Preserve Ejection Fraction
Authors: Toshinari Onishi, Katsuomi Iwakura, Masato Okada, Nobuaki Tanaka, Watanabe Heitaro, ATSUNORI OKAMURA, Masahiro Seo, Masamichi Yano, Takaharu Hayashi, Akito Nakagawa, Yusuke Nakagawa, Shunsuke Tamaki, Takahisa Yamada, Yoshio Yasumura, Yohei Sotomi, Shungo Hikoso, Daisaku D Nakatani, Yasushi Sakata
Journal: Circulation (2022)

Background: In patients with type 2 diabetes mellitus (T2DM), poor glycemic control is associated with higher risk of heart failure (HF) and cardiovascular death. On the other hand, the U-shaped relationship between HbA1c and mortality in T2DM patients with HF was reported by previous studies. The relationship between glycemic control and prognosis in patients with HF with preserved ejection fraction (HFpEF) is not fully elucidated. Methods: We enrolled 345 T2DM patients (80±25 years, Male 48.4%) registered in the PURSUIT-HFpEF (Prospective, Multicenter, Observational Study of Patients with Heart Failure with Preserved Ejection Fraction), a multicenter registration of patients hospitalized for decompensated HFpEF, between June 2016 and December 2020 for the present study. We performed echocardiography and measured HbA1c before discharge, and followed patients for median of 388 days (IQR 257-729 days) to observe the major adverse cardiovascular events (MACE; composite of death, HF hospitalization and stroke). We divided patients based on HbA1c into 5 groups (&lt;6.5%, 6.5-6.9%, 7.0-7.5%, 7.5-8.0% and &gt;8.0%). Results: There was no significant difference in age, gender, echocardiographic parameters among the groups. Cox proportional hazard model revealed that age (p=0.01) and HbA1c&lt;6.5% (p=0.01) were independent predictors for MACE, and hazard ratio (HR) for MACE in patients with HbA1c&lt;6.5% was 1.75 (95% CI, 1.10 to 2.77) comparing to those with HbA1c 6.5-6.9%. Patients with HbA1c&gt;8.0% tended to have higher incidence of MACE (p=0.076, HR 1.73 95%CI, 0.94 to 3.17). Conclusions: Among T2DM patients with hospitalized for HFpEF, HbA1c&lt;6.5 was associated with higher incidence of MACE, and there might be U-shaped relationship between HbA1c and MACE incidence.
Abstract 12775: The Major Contribution and Characteristics of Smooth Muscle Cell Foam Cells in Human Atherosclerotic Lesions Based on Flow Cytometry and Single Cell RNA Sequencing
Authors: Sima Allahverdian, Valentin Blanchard, Basak Sahin, Veronique Ollivier, Jean-Baptiste MICHEL, Gordon A Francis
Journal: Circulation (2022)

Background and Aims: Smooth muscle cells (SMCs) comprise the majority of cells within human atherosclerotic intima. Our previous study of human coronary atherosclerosis found that ≥50% of foam cells are of SMC origin and not primarily of macrophage origin as previously thought. In a recent investigation we reported that ~70% of all foam cells in ApoE-/- mice fed a Western Diet for 6 weeks are SMC-derived. In the current investigation we utilized flow cytometry and single-cell RNA sequencing to study the contribution and characteristics of SMC-derived foam cells in human atherosclerotic plaques. Hypothesis: SMCs comprise the majority of foam cells in human atherosclerosis and SMC foam cells have a unique gene expression pattern compared to macrophage foam cells. Methods: Formalin-fixed coronary and aortic samples were digested, stained with the lipid dye BODIPY and CD45 antibody and separated into CD45+ (leukocyte) and CD45- (non-leukocyte) foam cell and non-foam cell populations using flow cytometry. Pieces of fresh human coronary artery with adventitia removed were subjected to gentle digestion and isolated cells used for single-cell RNA Sequencing (n=3) using 10X Genomics Chromium Single Cell 3’ Reagent Kits v3 Technology. Results: Flow cytometric analysis indicates that approximately 65% of total foam cells of human coronary and aortic atherosclerotic lesions are of non-leukocyte origin. Unsupervised Seurat-based clustering (R version 4.2.0) singled out multiple cell clusters including SMCs, leukocytes, and endothelial cells in all 3 samples. Combining data resulted in identification of 15 distinct clusters including 8 SMC clusters ranging from well-differentiated to varying degrees of dedifferentiation. Combining multiple markers identified by in vitro and in vivo studies of SMC foam cells we were able to identify 2 possible SMC foam cell clusters with gene expression patterns distinct from macrophage foam cells. Conclusions: Our findings further identify SMCs as the major contributors of foam cells in atherosclerosis, and provide novel tools to investigate the nature of SMC foam cells in human atherosclerosis and their responses to anti-atherosclerotic therapies.
Abstract 14023: Myocardial Perfusion Abnormalities: A Potential Biomarker for Ventricular Arrhythmias in Hypertrophic Cardiomyopathy Young Patients?
Authors: Philippe Chevalier, Antoine Deliniere, Gilles MILLAT, Babken Asatryan, Alexandre Janin, Francis BESSIERE, Clement Boiteux, Christelle Haddad
Journal: Circulation (2022)

Introduction: Despite progress in the field, risk stratification for sudden death in patients with hypertrophic cardiomyopathy (HCM) remains challenging. Although ventricular arrhythmias (VA) account for most of these events, the mechanisms responsible for cardiac arrest in HCM are not understood. Hypothesis: Abnormalities in myocardial perfusion may create an arrhythmogenic substrate in HCM patients. Methods/ Results: A 12-year-old boy was admitted to our department after an out-of-hospital cardiac arrest, with documented ventricular fibrillation while running. A non-obstructive asymmetric HCM was diagnosed with echocardiography (max LV wall thickness 32 mm). He had one conventional risk factor for SCD. Genetic testing revealed a heterozygous state for a MYH7 variation: p.Glu500Ala (NM_000257.3:c.1499A&gt;C). This variation was classified as “probably pathogenic” (class 4 according to ACMG). His father and his 15-year-old brother were heterozygous for the same variant and were asymptomatic. The brother displayed a similar HCM phenotype. The patient received an implantable defibrillator and suffered from appropriate exercise-related shocks within 6-months despite sotalol therapy (160 mg bid). Because the VA occurred always when the patient was engaged in vigorous physical activity despite beta blocker and since he could not refrain from physical activity, thallium-201 myocardial scintigraphy was performed. To further understand the arrhythmogenic phenotype, his brother underwent the same investigation. Significant uptake perfusion defects in both initial and delayed images were evident in the proband (15%) but not in the asymptomatic brother. Treatment with antianginal drug (amlodipine 5 mg/day) was initiated. With 10 mg/day amlodipine was associated with a significant improvement of the scintigraphy (6% versus 15% perfusion defect). At a follow-up of 12 months, there was no recurrence of VA. Conclusions: Regarding HCM patients, the present report 1) strengthens the hypothesis that myocardial perfusion defects may identify patients at risk for VA, 2) suggests that tailored anti-ischemic prescription may be useful, and 3) underscores the need of prospective studies quantifying ischemia in HCM patients with exercise-induced VF.
Abstract 13995: Relationships Between Neighborhood Disadvantage and Cardiovascular Findings at Autopsy in Subjects With Sudden Death
Authors: Anne Cornelissen, Liang Guo, Sam J Neally, Leah Kleinberg, Ashley Forster, Rajeev Nair, Neel Gadhoke, Saikat Ghosh, Atsushi Sakamoto, Yu Sato, Rika Kawakami, Masayuki Mori, Kenji Kawai, Raquel Fernandez, Armelle Dikongue, biniyam Abebe, Robert Kutys, Maria Romero, Frank D Kolodgie, Yvonne Baumer, Tiffany M Powell-Wiley, Renu Virmani, Aloke Finn
Journal: Circulation (2022)

Introduction: Neighborhood disadvantage is associated with a higher risk of sudden cardiac death. However, autopsy findings have never been investigated in this context. Here, we sought to explore associations between neighborhood disadvantage and cardiovascular findings at autopsy in cases of sudden death in the State of Maryland. Methods: State of Maryland investigation reports from 2,278 subjects within the CVPath Sudden Death Registry were screened for street addresses and 9-digit zip-codes. Area Deprivation Index (ADI), used as metric for neighborhood disadvantage, was available for 1,464 subjects; 650 of whom self-identified as Black and 814 as White. The primary study outcome measurements were causes of death and gross and histopathologic findings of the heart. Results: Subjects from most disadvantaged neighborhoods ( i.e. , ADI ≥ 8; n = 607) died at younger age compared with subjects from less disadvantaged neighborhoods ( i.e. , ADI ≤ 7; n = 857; 46.07 ± 14.10 versus 47.78 ± 13.86 years; p = 0.02) and were more likely Black or women. They were, however, less likely to die from cardiac causes of death (61.8% versus 67.7%; p = 0.02) and had less severe atherosclerotic plaque features, including plaque burden, calcification, intraplaque hemorrhage, and thin-cap fibroatheromas. In addition, subjects from most disadvantaged neighborhoods had lower frequencies of plaque rupture (18.8% versus 25.1%, p = 0.004). However, these associations were omitted after adjustment for traditional risk factors and race. Conclusion: Neighborhood disadvantage did not associate with cause of death or coronary histopathology after adjustment for cardiovascular risk factors and race, implying that social determinants of health other than neighborhood disadvantage play a more prominent role in cardiovascular pathology.
Abstract 14282: Outcomes Following Aortic Valve Replacement Among Kidney Transplant Recipients. A Systematic Review and Meta-Analysis
Authors: Song Peng Ang, Jia Ee Chia, Vikash Jaiswal, Richa Mudwari, David Song, Tong Hong Chia
Journal: Circulation (2022)

Introduction: While kidney transplant recipients (KTR) are high risk candidates for valve replacements, the safety of transcatheter aortic valve replacement (TAVR) is limited among this population as they are excluded from major trials. We aimed to compare the outcomes between TAVR and surgical aortic valve replacement (SAVR) among KTR by a systematic review and meta-analysis. Methods: We comprehensively searched PubMed, Embase, and Cochrane Library from its inception until April 20, 2022 for relevant studies. Outcomes were pooled using the DerSimonian and Laird random-effects model and reported as odd ratios (OR) or standardized mean difference (SMD) and 95% confidence intervals (CI). Results: 6 studies involving 5,452 patients (1,956 TAVR, 3,496 SAVR) were included in the analysis. TAVR patients were older (69.4 years vs 62.8 years), were less likely to be male (66.7% vs 67.9%) and had a higher prevalence of most comorbidities including coronary artery diseases (78% vs 58%), heart failure (71% vs 42%) and diabetes mellitus (52% vs 45%). Compared with SAVR, KTR undergoing TAVR had significantly lower risk of in-hospital all-cause mortality (OR 0.51, 95% CI: 0.39 to 0.67, p&lt;0.001), acute kidney injury (RR 0.49, 95% CI: 0.34 to 0.71, p&lt;0.001), blood transfusion (OR 0.29, 95% CI: 0.19 to 0.55, p&lt;0.001) and a shorter length of hospital stay (SMD -0.67, 95% CI: -1.10 to -0.24, p=0.002). In contrast, there was a higher need for permanent pacemaker implantation among the TAVR cohort compared to SAVR cohort (OR 3.44, 95% CI: 2.67-4.43, p&lt;0.001). Conclusions: TAVR appeared to be a safe alternative compared to SAVR in KTR, with a lower rate of short-term mortality, AKI and length of hospitalization but a higher rate of permanent pacemaker implantation. Further studies are encouraged to study the long-term outcomes among these patients.
Abstract 14176: Assessment of Atrial Septal Defect Dynamic Changes Within the Cardiac Cycle With Cardiovascular Computed Tomography
Authors: Bibinaz Eghtedari, Luay Hussein Alalawi, April Kinninger, Venkat S Manubolu, Dhiran Verghese, Jairo Aldana-Bitar, Ahmed K Ghanem, Khadije Ahmad, Karla Sanchez, Sion Roy, Matthew Budoff, Priya Pillutla
Journal: Circulation (2022)

Objectives: Successful and safe percutaneous closure of atrial septal defects (ASD) is contingent upon the accurate measurement of defect size and adjacent rim tissue, as well as the spatial relationship to other cardiac structures. Previous studies utilizing three-dimensional echocardiography have found significant changes in ASD defect size throughout the cardiac cycle. Cardiac computed tomography (CT) provides excellent spatial and temporal resolution of cardiac structures. Our study examines the efficacy of cardiac CT as a modality for evaluating dynamic changes in ASD defect size throughout the cardiac cycle. Methods: Thirty patients with an ostium secundum ASD underwent cardiovascular CT imaging prior to percutaneous or surgical repair. Cardiovascular CT was performed with a multidetector scanner and images were analyzed using a GE Advantage Workstation capable of advanced image processing and manipulation. ASD defect size was measured in the axial, coronal, and sagittal views at (end-systolic phase) 35% and (end-diastolic phase) 95% of the cardiac cycle. Results: In 30 participants the mean defect size was not significantly different across the three planes, axial mean was 22.4±15.3, coronal 23.7±16.2, and sagittal at 22.3±16.9, p=0.923. However, the change in defect size during the cardiac cycle was significantly different in all three views, P&lt;0.0001 for all. On the axial view, the mean change from 35% to 95% was 6.5±4.9, while the coronal view change was 7.4±5.7, and the sagittal view change was 4.3±3.9. Additionally, the change in size increases with the defect size (figure 1). Conclusions: Cardiac CT imaging accurately depicts dynamic changes in ASD defect size throughout the cardiac cycle, and as such, may be considered a valuable and non-invasive imaging modality for patients undergoing pre-procedural evaluation.